title: Calcineurin inhibitor nephrotoxicity: a review and perspective of the evidence.
abstract: BACKGROUND
  There is no doubt that acute calcineurin inhibitor (CNI) nephrotoxicity exists; however, chronic CNI nephrotoxicity is questionable at best.
  
  
  METHODS
  We reviewed the literature to identify original articles related to the use of CNIs in renal and nonrenal solid organ transplantation in order to examine the available evidence about their chronic nephrotoxicity and contribution to graft failure.
  
  
  RESULTS
  Early clinical experience and animal studies support the evidence of CNI nephrotoxicity. These findings evolved into the dogma that CNI nephrotoxicity is the major cause of late renal allograft failure. However, in transplanted kidneys the specific role of chronic CNI nephrotoxicity has been questioned. The emerging literature clearly highlights the lack of solid evidence for the role of CNIs as the sole and major injurious agents that cause chronic renal dysfunction and subsequent graft failure. Most of the evidence available to date is against complete CNI avoidance, and minimization appears to be a more viable strategy. It is becoming increasingly clear that the typical pathological lesions linked to chronic CNI use are highly nonspecific, and most of the chronic changes that have been attributed to chronic CNI nephrotoxicity are the consequences of previously unrecognized immunologic injuries. One needs to keep in mind that the potential risk of side effects of CNI use should be balanced against the risk of rejection.
  
  
  CONCLUSIONS
  More research should focus on addressing the true causes of chronic graft dysfunction rather than focusing on the overexaggerated contribution of CNIs to late graft loss.
authors.affiliation: Division of Renal Diseases and Hypertension, University of Minnesota, Minneapolis, MN 55414, USA.
authors.forename: Naim
authors.initials: N
authors.lastname: Issa
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Kukla
authors.forename: Hassan N
authors.initials: HN
authors.lastname: Ibrahim
mesh_terms: D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000009:adverse effects; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016030:Kidney Transplantation / Q000276:immunology; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced*; D016559:Tacrolimus / Q000009:adverse effects; D014180:Transplantation; D014181:Transplantation Immunology
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus